(1) Abelson murine leukemia virus (Ab-MuLV) was shown to induce mast cell transformation by a nonautocrine mechanism in vitro when interleukin-3 (IL-3) was initially utilized to enhance the proliferation of the mast cell phenotype. Ab-MuLV was the only retrovirus analyzed that conferred factor-independence and leukemogenicity to the mast cell cultures. Ab-MuLV was also capable of inducing mastocytomas in vivo under specific conditions. These results define a new target for transformation by Ab-MuLV. (2) Human bone marrow cells were infected with ras-containing retroviruses pseudotyped with amphotroph (Am)-MuLV. No direct transformation of hematopoietic cells infected with these viruses was observed in long-term cultures. However, there was a significant increase in the emergence of Epstein-Barr virus (EBV)-positive pre-B cell lines from the virus-infected cultures which released virus and expressed the p21 transforming protein. (3) A recombinant murine retrovirus containing the erb B gene of avian erythroblastosis virus was generated and shown to induce transformation of NIH/3T3 and murine hematopoietic cells in vitro. Characterization of these transformants is currently underway. (4) Several retrovirus-transformed hematopoietic cell lines derived in our laboratory by transformation with various acute transforming retroviruses were analyzed to determine their phenotype and stage of differentiation by fluorescence activated cell sorter analysis of lineage-specific cell surface antigens and examination of their immunoglobulin and T cell receptor gene rearrangement patterns. The majority of the lines analyzed expressed characteristics of very immature B cells. However, certain lines appeared to be less differentiated. Preliminary evidence has indicated they may represent transformed counterparts of lymphoid or lymphoid/myeloid progenitor stem cells.